Establishing causal relationships between biopsychosocial predictors and correlates of eating disorders and their mediation by neural pathways

Lead Research Organisation: King's College London
Department Name: Social Genetic and Dev Psychiatry Centre


The eating disorders (EDs) [anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and related syndromes] are common psychiatric disorders that affect up to 15% of young women and up to 4% of young men in developed countries. The cause of these disorders is complex and their development influenced by environmental, psychological and biological factors that may interact to create a risk for different clinical presentations of the disorder. While known risk factors include sociocultural influences (e.g. media exposure, idealisation of thinness) and personality factors, a range of other factors are either unknown or can currently only be considered as correlates. There is also the increasingly broad acceptance of EDs as being brain-based disorders sharing neurobiological overlaps with anxiety disorders and addictions. Identifying true risk factors for EDs and understanding how they contribute to the development of the specific aspects of the disorders, including behaviours related to reward and punishment, cognitive control and emotional processes, will be crucial for improving prevention and treatment of EDs.

To investigate this and understand how behaviours of dysfunctional eating develop, we will use a rich database collected a large population-based, longitudinal cohort of adolescents of the IMAGEN study. With over n=2000 participants recruited from four European countries, including the UK, Ireland, Germany and France, and followed-up at ages 14, 16, 19 and 23, IMAGEN is the largest and most comprehensively characterized longitudinal gene x neuroimaging cohort. The adolescents of this study underwent neuroimaging assessments and extensive assessments to monitor health and wellbeing, including personality measures, social determinants, and pre- and post-natal life-events questionnaires, neuropsychological and biological measures. There is also an extensive characterisation of behavioural measures related to ED symptoms, internalising and externalising behaviours and substance use. To demonstrate that any differences observed in the IMAGEN population can also apply to a clinical population, we will complement the IMAGEN sample with a sample of emerging adults, of comparable age to the most recent IMAGEN follow-up (i.e. ~ 23 years-old), diagnosed with a first episode ED (AN or BN/BED). Before undergoing treatment for their ED, those individuals, unmedicated at the time of recruitment, will be assessed in a similar way as the IMAGEN participants. By combining these two samples we will be in a position to identify multiple correlates of dysfunctional eating across the full spectrum of drinking patterns. The analyses of the repeated measures of the longitudinal IMAGEN dataset, will allow us to better establish which correlates have a causal role in the development of EDs (those occurring before appearance of eating disorder symptoms). They will also enable us to characterising possible protective and/or additional risk factors, both environmental and biological.

For this research, we have brought together unique resources, a leading expert in EDs and scientific leaders in neuroimaging, genetics and developmental psychopathology to form a multi-disciplinary team, which is excellently positioned to deliver the research necessary to understand the underlying mechanisms and heterogeneity of EDs and inform future prevention and treatment strategies.

Technical Summary

This project aims to identify early biomarkers of eating disorders (EDs) by applying Big Data methods to the rich database derived from a representative population of adolescents and a clinical sample of emerging adults with a current or previous ED diagnosis.
First, we investigate causality of ED risk factors in the IMAGEN population cohort of n=2000 male and female adolescents followed-up at ages 14, 16, 19 and 23 years. We will investigate how biopsychosocial correlates and environmental risk factors such as adverse life events will influence these relationships and how their effects may be mediated by alterations in neural networks. Next, we will use machine learning procedures based on cross-validated regularised logistic regression combining neuroimaging, genomic and psychometric data modalities to identify correlates of EDs and select the features that best classify individuals who endorse ED symptoms along with those who endorse no ED symptoms at any time point. To identify predictors of ED symptoms, we will use age 14 IMAGEN data to compare individuals who developed ED symptoms over time (symptoms absent at age 14 but present at later ages), or those who recovered (symptoms present at age 14, not at later ages) to those who never developed symptoms. Finally, we will select the most predictive and easily applicable components of our comprehensive profile for validation in a clinical sample. These will be patients aged 18-25, with a 1st episode of DSM-5 AN or BN at first assessment (baseline) and followed-up with a second (after 2-years) assessment as well as patients fully recovered from a AN or BN diagnosis (n = 50 /diagnosis). All groups will be assessed through standardised protocols in a way identical to IMAGEN.
This paradigmatic multimodal approach, in which neuroimaging may provide added value compared with the existing standard assessments, may yield potential application for early and differential ED diagnoses.

Planned Impact

Adolescents who engage in persistently disturbed eating behaviours [from severe undereating/self-starvation to overeating/binge eating] and who initiate these behaviours early in life are at elevated risk for a range of negative outcomes that span emotional (anxiety and mood disorders), behavioural (self-harm, and substance use), social (poor peer, family and personal relationships), physical (death through malnutrition, obesity and related complications), educational (poor academic performance) and economic (reduced employability) impacts. Even sub-clinical syndromes are associated with negative health outcomes. Early diagnosis and prognosis of eating disorders (EDs) would be key to improving current treatments. The aetiology of EDs is however complex, with evidence for multiple overlapping and distinct biopsychosocial factors implicated in risk for different clinical EDs and/or subclinical disordered eating.

This project will likely lead to an increasing knowledge base about the aetiology and development of eating disorders. By comprehensively exploring biopsychosocial risk factors and biomarkers for EDs. Our paradigmatic approach that uses a wide range of data modalities, in which neuroimaging may provide added value, compared with the existing standard assessments, may have application for early and differential ED diagnoses, making a significant contribution to prediction and re-classification of EDs. The identification of biomarkers for early diagnosis and prognosis based on brain networks will allow implementation of pre-existing intervention programmes at an earlier stage. It will also facilitate development of novel early intervention programmes, which target specific neurobehavioural phenotypes. Our longitudinal assessments of ED symptoms trajectories will establish what measures of brain or other features are associated with persistent disordered eating and provide information inform about reversibility of symptoms. The results of the project are thus preparing for future work identifying novel targets, as well as for the establishment of neurobehaviourally informed endpoints for interventions that alleviate the societal and economic burden of disease.

This project will also achieve considerable impact by increasing the economic competitiveness of the United Kingdom. The young scientists working on this project will be trained in other parts of Europe and in the USA by experts and world leaders in the field of neuroimaging, genetics and statistics. Development of such skills and networking with the best scientists at this early stage of their career will provide optimal conditions to foster the next generation of leaders and economic performance of the UK.


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Description Eating Disorders: Delineating illness and recovery trajectories to inform personalised prevention and early intervention in young people (EDIFY)
Amount £3,913,565 (GBP)
Funding ID MR/W002418/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 08/2025
Description Zuo's Fellowship
Amount £301,901 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 06/2021 
End 06/2024
Description environMENTAL
Amount € 9,972,288 (EUR)
Organisation Charite Campus Virchow-Klinikum 
Sector Academic/University
Country Germany
Start 08/2022 
End 08/2027
Title ESTRA Database 
Description In this cohort study, we propose to investigate biological and environmental factors shape brain function and behaviour in distinct ways, leading to specific risk constellations and neurobehavioural trajectories for eating disorders. Data collected from newly recruited patients with a current or past diagnosis of Anorexia Nervosa or Bulimia Nervosa and their controls will include comprehensive assessments to monitor mental health and wellbeing in participants with an age range of 18-25 years. Assessment instruments and protocols have been selected to allow direct comparison to IMAGEN. These include personality measures, social determinants, and pre- and post-natal life-events questionnaires. Assessments of weight, height and pubertal development were also included. Neuropsychological measures include IQ and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB). There is also an extensive characterisation of behavioural measures related to internalising and externalising behaviours and substance use. Clinical phenotypes were indexed using the Development and Wellbeing Assessment (DAWBA) and Strengths and Difficulties Questionnaire (SDQ). ED symptoms were measured by 47 items in the DAWBA. Further details can be found in. At age 23, the Eating Disorder Examination Questionnaire (EDE-Q-6), the Three Factor Eating Questionnaire (TFEQ-R 18) and the MINI International Neuropsychiatric Interview are also used to assess symptoms and clinical phenotypes. Blood samples have been collected to allow future analyses of differential DNA methylation, and genetic variations based on large GWAS meta-analyses. We are depositing our newly collected data to the centralised IMAGEN databank that is localised at Neurospin, CEA, France. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Access to world-class infrastructure: The data deposited to centralised IMAGEN databank will facilitate access to world-class infrastructure and supports big data analytics, management and distribution of programs and research tools. This databank that integrates all the data modalities assessed will be remotely accessible for interested researchers on a collaborative basis. In this way, we expect our work to form an important knowledge base for researchers in several fields within and across discipline. 
Description EDIFY 
Organisation King's College London
Department Department of Psychological Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Research Project titled: Eating Disorders: Delineating illness and recovery trajectories to inform personalised prevention and early intervention -EDIFY The overarching aim of this project is to transform the way in which eating disorders (ED) are identified, prevented, and treated. We hope to support young people to come forward for help and to give them the tools they need to recover more quickly. We will spearhead the development of inclusive, evidence-based ED policy and practice. With expertise in recruitment, acquisition and analysis of data from longitudinal cohorts acquired through the management of the ESTRA, STRATIFY and IMAGEN studies, I will lead analyses specifically aimed at developing and testing predictive models of risk and resilience for eating disorders and associated high-risk behaviours in young people.
Collaborator Contribution Eating disorders have complex aetiology, spanning neurobiological, genetic, psychological, social and cultural factors. Thus, transdisciplinary research is essential. Our group bridges disciplinary silos i.e. child and adult psychiatry/psychology; translational research; bioinformatics; intervention development; early intervention; schools-based interventions; neurobiology; genetics, longitudinal cohorts; epidemiology; psychosocial ED risk; arts- and design-led research; policy; and advocacy. Several of us have successfully collaborated on large scale research. We are a diverse group of academics in terms of gender, ethnicity, nationality and career stage, and have strong partnerships with YP advisory groups, YP with lived experience of an ED and with carers/families.
Impact - Funding from the Medical Research Council: Funded Value £3,913,565 - multi-disciplinary collaboration including child and adult psychiatry/psychology; translational research; bioinformatics; intervention development; early intervention; schools-based interventions; neurobiology; genetics, longitudinal cohorts; epidemiology; psychosocial ED risk; arts- and design-led research; policy; and advocacy.
Start Year 2021
Description environMENTAL 
Organisation Charite Campus Virchow-Klinikum
Country Germany 
Sector Academic/University 
PI Contribution I am member of the international environMENTAL consortium, a new an ambitious project funded by the European Commission aiming at reducing the impact on citizens and patients of major environmental challenges that change society in Europe and globally, including urbanicity, climate/pollution and psychosocial stress following the COVID-19 pandemic, With expertise in genetics and biological psychiatry, I lead aspects of the project specifically related to the identification and characterisation of molecular and neurobiological processes underlying mental illness related to these environmental changes. I also provide access to data collected in the ESTRA, STRATIFY and IMAGEN projects to study collaborators.
Collaborator Contribution This project also brings together an interdisciplinary team of experts from 22 partner or associated institutions around the world, uniquely qualified to deliver our research. This also provides access to data that will enable us to leverage and federate the largest European population cohorts of over 1.5M individuals, as well as clinical and global cohorts.
Impact - Funding (EUROS 10 millions) from the Horizon Europe Work Programme 2021-2022: "HORIZON-HLTH-2021-STAYHLTH-01-02: Towards a molecular and neurobiological understanding of mental health and mental illness for the benefit of citizens and patients" - Multidisciplinary collaboration involving neuroscientists, psychiatrists, geo-scientist, climatologists, psychologists, epidemiologists, anthropologists, sociologists, computer scientists, experts in digital interventions as well as non-academic stakeholders.
Start Year 2021
Description Youth advisors-Study participants 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Engaging study participants with newsletters communicating research findings in relation to eating disorders; blogs around eating disorders. This involved undergraduate students and youth advisors with a history of eating disorders. The later gave us feedback on our newsletters and commented on our research methodology and findings.
Year(s) Of Engagement Activity 2021,2022